Theoretical study of heptadentate bispidine ligands for radiopharmaceutic applications

The complexes of radiopharmaceutically relevant trivalent metals (MIII = InIII, BiIII, LaIII, LuIII, AcIII) with two heptadentate bispidine-based ligands (L) have been investigated by DFT calculations. The main questions included the encapsulation efficiency of the ligands for the different-size metals, the differences in bonding, the possibility and characteristics of octa- and nonacoordination achieved by attachment of H2O ligands to the ML complexes as well as the thermodynamic stabilities under isolated and aqueous solution conditions. The results supported high efficiencies of the ligands resulting in very good stabilities of the complexes. The bonding analysis revealed small differences based on a gentle interplay of the sizes and electronic structures of the MIII ions as well as on the difference in two donor groups of the ligands. The present heptadentate ligands form tighter interactions with the metals as compared to the octadentate derivative, and leave less space for coordination of additional ligands.